Table 7.
Polypeptide- and protein-based nanosystems with salinomycin.
| Composition | Combination Therapy | Preparation Method | Size (nm) | PDI | Zeta Potential (mV) | EE (%) | Drug Loading (%) | In Vitro Release | Biological Effect | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| TAT protein | - | Conjugation through a photosensitive linker; attachment of solubilizing sugar moiety by click chemistry | n.r. | n.r. | n.r. | n.r. | n.r. | Complete release upon irradiation at ≥ 365 nm within 80–100 s. | More that 4-fold reduction in IC50 values by conjugation with TAT protein in MCF-7 and JIMT-1 breast cancer cells, compared to free Sali | [41] |
| Elastin-like polypeptide (iTEP), DMHA, α-tocopherol | - | Conjugation through a chemical reaction | 179.9 | n.r. | +0.046 | 75.4 | n.r. | 100% in PBS pH 7.4, at 24 h | Similar cytotoxicity with free Sali in 4T1 mammospheres; slower clearance and 2.4-fold greater tumor accumulation in vivo, but lower accumulation in heart and lung, than free Sali; 1.1-fold reduction in CSC frequency in tumor-bearing mice | [42] |
| Elastin-like polypeptide (iTEP) | PTX 1 | Conjugation 2 through a chemical reaction | 85.09 | n.r. | n.r. | 84.6 3 | n.r. | Half-life of 12.15 h in 0.1 M sodium acetate- acetic acid buffer pH 5.0/4.67 h in PBS pH 7.4 4 | 30-fold increase in AUC, 35-fold increase in elimination half-life and 3.4-fold increase in tumor accumulation by incorporation into NPs than free Sali; greater inhibition of primary 4T1 breast tumor and metastasis by Sali-ABA NPs compared to free drug; the combination therapy with PTX slowed down tumor growth and improved overall survival of mice more efficiently | [49] |
| Silk fibroin | PTX 5 | Nanoprecipitation, ultrasound-induced cross-linking 6 | 241.0 7 | 0.147 7 | −14.24 7 | 34.7 7 | 12.1 7 | 94.5% in PBS, at 24 h, 98.3%, after 5 days/17.5% in PBS + 0.5% Tween 80, after 30 days 7,8 | Reduction in Sali toxicity by incorporation into NP; locoregional dual drug SF gel administration produced smaller tumors in H22 tumor-bearing mice, compared to systemic administration of dual drug SF gel and single drugs; effective anti-CSC effect in vivo; dual drug SF gel showed superior tumor growth inhibition effect and longer survival of mice than other treatments | [96] |
| Keratin, vitamin E acetate | Ce6 | Nanoprecipitation | 127 | 0.13 | −27 | n.r. | n.r. | 100% in PBS pH 6.8 + Tween 80, after 7 h | Synergistic effect in MCF-7 and MDA-MB-231 breast cancer cells; reduction in Sali dosage; incorporation into keratin NPs reduced mammosphere formation efficiency, compared to free drugs | [97] |
PDI, polydispersity index; EE, entrapment efficiency; TAT, trans-activator of transcription protein; n.r., not reported; Sali, salinomycin; DMHA, N,N-dimethylhexylamine; CSC, cancer stem cell; PTX, paclitaxel; AUC, area under the curve; NP, nanoparticle; SF, silk fibroin; Ce6, chlorin e6. 1 Salinomycin and paclitaxel were co-loaded into the nanoparticles. 2 Salinomycin was modified by conjugation with a pH-sensitive linker (4-(aminomethyl)benzaldehyde, ABA), yielding salinomycin-ABA. 3 Data reported for paclitaxel. 4 Data reported for salinomycin-ABA and paclitaxel, respectively. 5 Paclitaxel was loaded into silk fibroin nanoparticles separately from salinomycin. 6 Data reported for the preparation of silk fibroin nanoparticles and nanoparticle-loaded silk fibroin gel, respectively. 7 Data reported for salinomycin-loaded silk fibroin nanoparticles prepared with a silk fibroin concentration of 15 mg/mL and salinomycin amount of 6 mg. 8 Data reported for salinomycin and paclitaxel, respectively (from the hydrogel).